Cytokines and chemokines differentially regulate innate immune cell trafficking during post kala-azar dermal leishmaniasis
| Autor: | Ashish Kumar Singh, Vijaya Mahantesh, Manas Ranjan Dikhit, Pradeep Das, Sanjiva Bimal, Shyam Naryan, Vidya Nand Rabi Das, Neena Verma, Ajay Amit, Shubhankar K. Singh, Krishna Murari Pandey |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Chemokine Adolescent Neutrophils medicine.medical_treatment 030231 tropical medicine Leishmania donovani Biochemistry 03 medical and health sciences Young Adult 0302 clinical medicine parasitic diseases medicine Humans Child Molecular Biology Post-kala-azar dermal leishmaniasis Innate immune system biology business.industry Leishmaniasis Cell Biology Middle Aged biology.organism_classification medicine.disease Immunity Innate 030104 developmental biology Visceral leishmaniasis Cytokine Integrin alpha M Gene Expression Regulation Immunology biology.protein Cytokines Leishmaniasis Visceral Female Chemokines business |
| Zdroj: | Journal of cellular biochemistry. 119(9) |
| ISSN: | 1097-4644 |
| Popis: | Post kala-azar dermal leishmaniasis (PKDL) is often considered to be the anthroponotic reservoir of visceral leishmaniasis (VL) in India. A better understanding of the host immune-response in dermal lesions of PKDL patients is therefore of utmost significance to minimize such patients and to restrict VL transmission. Although the innate immune response is known to play an important role in parasite clearance from dermal lesions, the actual contribution of innate cells to the pathogenicity of PKDL is poorly understood. The present study explored the immune-pathogenesis of PKDL patients to understand the expression of CD62L, CD11b, CXCL8/IL-8, and MIP1-α and their contribution in signaling during innate cell trafficking. Twenty-five individuals were enrolled, who comprised eight active and untreated macular cases, seven active and untreated cases with papulo-nodular PKDL manifestations, five successfully treated post PKDL cases and five healthy individuals from a non-endemic region of Bihar, India. The immunological investigation was performed on biopsy specimens prepared with a disaggregation technique and blood samples. We observed that the PMNs in nodular patients displayed decreased L-selectin (CD62L) levels and increased integrin (CD11b) expression compared with those in macular patients. Further analysis showed that lower PMN extravasation in macular patients occurred because of inadequate CXCL8/ IL-8 release. In summary, Leishmania donovani (L. donovani) infection in macular PKDL patients decreased leucocyte rolling (L-selectin shedding) and induced up-regulation of the cellular signaling factors involved in pathogenesis (ERK1/2) as well as down regulated the signaling elements (p38 MAPK) involved in the Th1 response, especially in PMNs. |
| Databáze: | OpenAIRE |
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